Aging and autoimmune disorders are often associated and share certain immune abnormalities suggesting common or related underlying defects. The aim of this proposal is to determine the causes for longevity in murine models for systemic autoimmune diseases with particular emphasis on the mechanisms responsible for the occurrence of sporadic long-lived individuals (approximately 4 times expected life span) in otherwise early- dying MRL-1pr/1pr and male BXSB lupus mice. To this end, we will determine whether longevity in these mice has genetic causes which would allow us to establish long-lived, coisogenic sublines carrying the mutated gene, or results from environmental factors or random somatic events. In the latter, attempts will be performed to clarify the molecular nature of the respective factors and events. To establish whether long-lived mice develop autoimmune symptoms and/or disease, serologic, pathologic, and histopathologic parameters associated with longevity will be established and compared with those from short- lived mice, and from the late-life lupus strains MRL-+/+ and female BXSB. Finally, because of the involvement of endogenous murine retroviruses in lupus-associated immune responses, certain lymphoproliferative disorders, and mutagenesis, we will investigate whether longevity is associated with or caused by differential retroviral insertion into germline or somatic DNA and/or results from differences in retroviral gene expression.